The Effects Of Bronchodilator Therapy On Respiratory And Autonomic Function In Patients With Familial Dysautonomia
|ClinicalTrials.gov Identifier: NCT01987219|
Recruitment Status : Completed
First Posted : November 19, 2013
Results First Posted : June 2, 2016
Last Update Posted : June 2, 2016
|Condition or disease||Intervention/treatment||Phase|
|Familial Dysautonomia||Drug: Albuterol-sulphate Drug: Ipratropium-bromide Other: placebo||Phase 3|
Familial dysautonomia (FD) is a rare fatal autosomal recessive disease caused by a deficiency of the protein IKAP.1 This results in a selective developmental defect that affects mostly afferent (sensory) neurons including those in the dorsal root ganglia and cranial nerves.2, 3 We have shown recently that the protein deficiency impairs the development of afferent baroreceptor pathways, leaving the sympathetic efferent neurons reduced in number but functionally active. This results in the complete failure to detect and buffer fluctuations in blood pressure leading to volatile hypertension. In addition to the afferent baroreflex pathways, the deficiency of IKAP during embroyogenesis also affects the function of the chemoreflex pathways. As a result, patients fail to increase ventilation adequately in response to hypoxia and hypercapnia.4 As well as the impairment of the neurological mechanisms that regulate breathing, patients with FD also have a combination of obstructive, restrictive and probably also neuromuscular lung disease. Failure to coordinate swallowing results in recurrent bouts of aspiration pneumonia occurring from birth.5, 6 Imaging studies show that almost all patients with FD have bronchial wall thickening, atelectasis and almost 30% have bronchiectasis7. Pulmonary function tests show air flow limitation and associated lung restriction with reduction in diffusion capacity12. Sudden attacks of asthma like wheezing are common 8 and frequently associated with emotional upset,5 a time when sympathetic outflow to the vasculature is increased heightened.3 There is also a component of restrictive lung disease, with a very high incidence of scoliosis, which frequently begins at an early age. Complicating matters further, many patients opt to undergo spine fusion surgery, 9 which could potentially worsen further chest wall compliance.10 Patients with FD also lack muscle spindles, 2 making it likely that they have neuromuscular abnormalities arising from the absence of proprioceptive feedback from the respiratory muscles involved in the coordination of breathing.
Severe respiratory disease is a leading cause of death in patients with FD and many are treated empirically with inhaled bronchodilators. It is not known, however, whether these drugs are effective at reversing increased airway resistance. Hence, there is an urgent need to understand if the short acting beta-2-adrenergic agonist albuterol and the anticholinergic ipratropium, are effective bronchodilators. Furthermore, because treatment with these agents has potential cardiovascular side effects, we will also analyze their effects on blood pressure, heart rate and cardiac output.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||The Effects of Bronchodilator Therapy On Respiratory and Autonomic Function in Patients With Familial Dysautonomia|
|Study Start Date :||March 2013|
|Primary Completion Date :||December 2014|
|Study Completion Date :||December 2014|
Active Comparator: Albuterol-sulphate
Albuterol-sulphate (Proventil ®) Beta-2-adrenergic agonist 2.5 mg 3 cc inhalation Peak effect 15 - 30 mins. Mean duration of effect 3 hours
Beta-2-adrenergic agonist 2.5 mg 3 cc inhalation Peak effect 15 - 30 mins. Mean duration of effect 3 hours
Other Name: (Proventil ®)
Active Comparator: Ipratropium-bromide (Atrovent ®)
IpratroAnti-cholinergic(Atrovent ®) 500 mcg 3 cc inhalation Peak effect 30 - 90 mins. Duration of effect 2 - 4 hours.pium-bromide
Anti-cholinergic 500 mcg 3 cc inhalation Peak effect 30 - 90 mins. Duration of effect 2 - 4 hours.
Other Name: (Atrovent ®)
Placebo Comparator: Placebo
Placebo Saline solution 3 cc NA
Saline solution 3 cc NA
- Change From Baseline of Forced Vital Capacity [ Time Frame: Pre and 30 minutes post study drug administration ]FVC is a measure of the amount of air exhaled, and is measured in liters of air per second. The percentage in the change in the amount of air exhaled from baseline, measured in liters of air per second. Increase in the percentage of air exhaled from baseline indicates improvement in respiratory function.
- Change in Respiratory Function (Airway Resistance at 5 Hz) From Baseline [ Time Frame: Pre and 30 minutes post study drug administration ]The percentage change in respiratory function from baseline is measured in percentage change in Resistance, kPa/(L/s).
- Change in Forced Expiratory Volume (FEV) From Baseline [ Time Frame: Pre and 30 post study drug admistration ]Forced expiratory volume is measured in liters of air per second. FEV was measured during the first second of exhalation.
- Change in Forced Expiratory Flow Between 25-75% (FEF25-75) [ Time Frame: pre and 30 minutes post intervention ]FEF25-75 is measured in liters of air per second at 25-75%
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01987219
|United States, New York|
|NYU Medical Center|
|New York, New York, United States, 10016|